The lower and upper incisors of female rats were repeatedly reduced every 48 hr for 21 days. A marked enlargement of the submandibular glands was observed at the end of this period. One day after the final reduction, dose dependent curves to phenylephrine and isoproterenol were obtained in relation to salivary flow rates. Secretory responses, expressed as mg/gland, showed that the dose response curve to the alpha1-adrenomimetic drug was not modified by treatment while that for isoproterenol was shifted to the right of the control. When the responses were expressed as microg of saliva/mg of wet tissue, the dose-response curve to both agonists was shifted to the right in the incisor-reduced group. (Activation of alpha2-adrenergic receptors by clonidine did not inhibit the responses to phenylephrine in the incisor-reduced rats.) Radioligand binding assays of alpha1-, beta- and alpha2-receptors did not show differences between control and experimental glands in terms of densities (Bmax) or affinities (Kd). The lack of correlation between the decrease in alpha2- and beta-mediated responses and the radioligand bindings suggests that postreceptor mechanisms are involved in the diminished secretory responses of the rat submandibular gland after periodic reduction or amputation of incisors.